1. Innate Host Defense Mechanisms
Hugh B.Fackrell
Filename: InnateM.ppt

2. Content Outline Definitions Nonspecific Exterior Defenses
Nonspecific Interior Defenses
Soluble factors
Lysozyme, interferon, complement
Cells
Phagocytes, natural killer cells
Inflammation
chemotaxis, diapedisis, phagocytosis
Assigned Readings
Innate immunity 6-11
Phagocytosis 65,68,467
Phagocytic defiiences
Inflammation 357,
Complement
Lysozyme 8, 10
Interferon (INF) , ,
Tumour necrosis factor (TNF)
NK Cells
NK Cells and TNF 391
Phagocytic deficiencies

3. Innate Immunity: Definition
AKA non adaptive immunity
AKA natural immunity
Non specific
Always Present
Present at birth
Those factors that are ALWAYS present to defend the body against infection

4. Adaptive Vs Innate Immunity

5. Innate vs Acquired Immunity
Respond to ALL microbes
Equally
consistently
ACQUIRED
respond AFTER exposure to:
microbe
virulence factor

6. Virulence Factor
A structural or physiological character that enables a microbe to cause disease
Breaches Innate Defenses

7. Exterior Defenses Skin Mucous membranes Eyes Outer Ear Canal
Alimentary Canal
Respiratory Tract

8. Respiratory Tract Defenses
Nasal hairs
nasal turbinates
mucus secretions
cough reflexes
ciliated epithelium
macrophages
phagocytosis

9. Exterior Defenses

10. Interior Defenses: Soluble Factors
Lysozyme
Interferon
Complement
Cells
Inflammation

11. Lysozyme

12. Interferon

13. Complement functions

14. Alternate Complement Pathway
Activated by:
endotoxin
human IgA
microbial polysaccharides
Effects
opsonic activity
chemotaxis of leucocytes
enhanced permeability of microbe
cytolysis

15. Interior Defenses: Cells
Soluble Factors
Cells
Natural killer cells
Phagocytes
Inflammation

16. Null Cell

17. Cytoxic T Cell

18. Perforin Pores

19. Cytotoxic cell: Pore formation

20. Phagocytosis

21. Tissue phagocytes - macrophages
liver -- Kupffer cells
neural -- microglial cells
connective tissue -- histiocytes
blood -- monocytes
spleen -- dendritic macrophages

22. Phagocytes: Distribution

23. Monocyte

24. Neutrophil

25. Mechanism of Phagocytosis
Attachment
Ingestion
Phagosome
Phagolysosome
destruction
Ejection

26. Macrophage Pseudopodia

27. Neutrophil phagocytosis

28. Phagocytosis

29. Mechanisms of Phagocytosis (1/3)
macrophage
bacteria
lysosomes
phagosome
nucleus
1) Attachment of bacteria
macrophage
bacteria
lysosomes
phagosome
2) Ingestion
nucleus

30. Mechanisms of Phagocytosis (2/3)
macrophage
lysosomes
phagosome
nucleus
3) phagosome engulfs bacteria
macrophage
lysosomes
4) formation of phagolysosome (lysosome with digestive enzymes joins phagosome)
phagosome
nucleus

31. Mechanisms of Phagocytosis (3/3)
macrophage
lysosome
phagolysosome
nucleus
5) Destruction of ingested microbes
macrophage
lysosome
phagolysosome
nucleus
6) Ejection of digested particles

32. Inflammation

33. Interior Defenses: Inflammation
Soluble Factors
Cells
Inflammation
Chemotaxis
Diapedesis
Phagocytosis

34. Leucocyte adherance

35. Chemotaxis

36. Diapedesis

37. Acute Inflammation C Reactive Protein
indicator of inflammation
CRP produced by IL-1 stimulation of the liver
CRP complexes with the polysaccharides of many bacterium and fungi
activates the alternative complement pathway which promotes phagocytosis
IL-1, TNF, interferon - act on the hypothalamus to induce fever

38. Acute Inflammation swelling, redness, heat and pain
foreign body such as a micro-organism invades the tissues
brief contraction of the blood vessels
vasodilation

39. vasodilatation - increases blood flow
swelling produces leaks - vascular permeability
fluid and red blood cells (erythrocytes) enter tissues producing redness
tissues swell with this influx; pressure & pain
heat from several sources
white cells (leukocytes):
a) neutrophils margination - clinging to vessel walls
b) squeeze out through the widened pores due to changes in microvascular structure.

40. Acute Inflammation - cont
neutrophils travel to injury site, attracted by chemotactic agents
activated leukocytes produce toxic substances and proteases. Chemical mediators triggered.
activation of complement C3 properdin
mast cells release histamine
clotting mechanism initiated

41. Pre Formed Chemical Mediators of Inflammation
Properdin: Stabilizes complement
Complement: present in normal serum and activated by convertase or immune complex
Histamine: inside the granules of mast cells
Serotonin: 5-hydroxy tryptamine (hormone and neurotransmitter) found in blood platelets and produces vasoconstriction
Lysosomal enzymes: lysosome in macrophages

42. Chemical Mediators of Inflammation: De novo Synthesis
Prostaglandin: mediate all aspects of inflammation
Leucotrienes: mediate all aspects of inflammation
Platelet: activating factors
Cytokines: modulate immune system; not antigen specific
Nitric oxide
Bradykinin: activated by Hageman factor; dilates arterioles

43. Cytokines Monokines: macrophages and monocytes
interleukin 1 (IL-1) and tumor necrosis factor (TNF)
e.g. lymphokines & lympocytes interleukin 2 (IL2), interferons and colony stimulating factors of T lymphocytes
Interferons are low molecular weight glycoproteins activated by viral infections
Autocrines - act on the cells producing them
Paracrines - act on neighbouring cells
Endocrines - act cells distant from the synthesizing cell
In inflammation:
act locally on the endothelium; promote leucoycte adherence
participate in acute phase reactions
act on fibroblasts
increase bloodclots on the endothelium

44. Cytokines - TNF promotes 1) inflammation Mediators:
neutrophil aggregation and activation
escape of proteolytic enzymes from mesenchymal cells which promotes tissue injury
1) inflammation
2) infection
3) tissue injury
4) neoplasm (rare)
Mediators:
IL-1, IL-6, TNF, prostaglandin (PGE) & interferons